Lecture 13: Evasion of Immune Responses

Question 1

What are the 3 ways a pathogen can evade a host’s immune response?

Answer 1

1. antigenic variation
2. latency
3. subversion of host response/molecular mimicry

Question 2

What is antigenic variation?

Answer 2

Pathogen displays new Ag that are not recognized by an immune response previously formed against this pathogen

Question 3

T or F: Antigenic variation allows a pathogen to evade a new immune response launched by a host.

Answer 3

False: it allows them to evade PRE-FORMED memory immune responses

Question 4

How many different serotypes does S. pneumonia have?

Answer 4

84

Question 5

What is the significance of the ability for pathogens to have many serotypes? (In terms of host recognition/response

Answer 5

The host has to launch a new Ab response to each serotype in order to clear the infection. This allloews a single pathogen to infect the same person over and over again.

Question 6

T or F: Serotypes of pathogens ensure that the pathogens (almost) always have a host.

Answer 6

True

Question 7

What is the difference between antigenic drift and antigenic shift?

Answer 7

Antigenic drift results from slight changes in a pathogen’s antigenic determinants.

Whereas an antigenic shift causes a much larger/more radical change in the antigenic determinants.

Ag drift only requires an altered B cell response (T cell response is still viable) while Ag shift requires new B and T cell response to be launched
(if not completely new T cell response, a mostly new)

Question 8

Identify the flowing as characteristic as belonging to either antigenic drift or shift:

Caused the H1N1 epidemic

Answer 8

shift

Question 9

Identify the flowing as characteristic as belonging to either antigenic drift or shift:

Caused by mutation in pathogen’s genome

Answer 9

drift

Question 10

Identify the flowing as characteristic as belonging to either antigenic drift or shift:

T cells response can still protect the host

Answer 10

drift

Question 11

Identify the flowing as characteristic as belonging to either antigenic drift or shift:

Causes seasonal flu epidemics

Answer 11

drift

Question 12

Identify the flowing as characteristic as belonging to either antigenic drift or shift:

When initially infected by a viral pathogen, NK cells are the only cells killing infected cells.

Answer 12

shift

Question 13

Identify the flowing as characteristic as belonging to either antigenic drift or shift:

Caused by recombination of viral gene segments

Answer 13

shift

Question 14

Identify the flowing as characteristic as belonging to either antigenic drift or shift:

Caused by recombination of viral gene segments

Answer 14

shift

Question 15

Identify the flowing as characteristic as belonging to either antigenic drift or shift:

Results in a virus expressing a completely new hemagglutinin or neuraminidase

Answer 15

shift

Question 16

Identify the flowing as characteristic as belonging to either antigenic drift or shift:

Requires a secondary non human host prior to infecting humans

Answer 16

shift

Question 17

Identify the flowing as characteristic as belonging to either antigenic drift or shift:

Requires new T helper response

Answer 17

Shift

Question 18

Describe the process of antigenic drift in the influenza virus.

Answer 18

A person has previously infected by a pathogen. Therefore this pathogen cannot infect his or her cells. This same pathogen acquires a mutation that produces a slightly altered hemagglutinin or neuraminidase. This “mutated” virus is not recognized by the person’s Ab response and is therefore able to infect his or her cells.

Question 19

Describe the process of antigenic shift in the influenza virus.

Answer 19

An animal (such as a pig) becomes infected with 2 viruses of different animal origins (such as human and avian). The segmented genomes of these 2 viruses become shuffled and packaged together (in new combinations). This novel virus expresses hemagglutin or neuraminidase that is not recognized by a human’s T or B memory memory cells → infection!

Question 20

Describe the antigenic variation that allows Trypanosome to evade a host’s immune system.

What the term for this mechanism?

Answer 20

Trypanosome has a cassette system of 1000s of genes that code for a variable surface glycoprotein (VSG) coat. The pathogen expresses a single VSG at a time, and once the host’s immune system has “successfully” killed the parasite, it switches VSGs. The host must then launch a new B (and T??) cell response allowing the parasite to replicate and thrive again. → many cyclical periods of trypanosome replication while evading host cell immune response

This is known as PROGRAMMED REARANGEMENT

Question 21

What disease does trypanosome cause?

Answer 21

African sleeping sickeness: creates many immune complexes that are deposited in the vasculature → damage to the vasculature all over the body → damages neural tissue → death

Question 22

Does the typical disease syndrome resulting from infection with a genetic drift variant differ from that caused by a genetic shift variant of Flu? Explain why or why not.

Answer 22

Yes. A genetic drift variant would cause a MILDER disease because of existing memory T cell responses in people that have been previously infected. The flu will be cleared much FASTER too.

Question 23

What is a state adopted by viruses in which they have entered the cells but do not replicate.

Answer 23

Latency

FYI TB can exhibit latency, so I don’t think it is unique to viruses

Question 24

Describe a latent virus (in general terms, not a specific type).

Answer 24

It infects a host cell and integrates its genome into the host genome. For a period of time, no pathogen proteins will be made (meaning there won’t be anything to present to T cells) or secreted (meaning there wont be anything to prime a B cell response). Once the virus becomes reactivated, viruses are made and secreted.

Question 25

While a virus is latent, it does not cause the host cell to make or secrete viral proteins. How is this significant?

Answer 25

The virus goes undetected by the host’s immune system. When proteins that are made, they are packaged onto MHC to be presented to T cells. And when they are secreted, they B cell response is able to be primed. Since this is not happening, B and T cells are not activated against the virus

Question 26

T or F: viruses in the latent phase can infect other hosts.

Answer 26

False. They can only infect once they have been reactivated

Question 27

Describe the “cycle” the herpes virus uses to evade a host’s immune system.

Answer 27

• Once a virus infects an area of tissue (primary infection) it begins to replicate.
• Some of the viruses travel down neurons and into the trigeminal ganglion where the virus integrates into the host genome.
• It is now in the latency phase.
• Once the virus is reactivated (mechanism is not understood but stress and sunlight are though to trigger it) it travels back down the the same nerve to (usually) the primary site of infection and the cycle continues.

Question 28

How does Varicella zoster virus evade a host’s immune system?

Answer 28

Latency
It is the virus that causes chickenpox/shingles and can be reactivated along ONE nerve pathway = why it is seem on one half of the body

Question 29

What viruses inhibit humoral immune response? What mechanism do these viruses specifically use?

Answer 29

1. Herpes simplex cytomegalovirus: encode FcR homologs that bind up Ab to interfered with phagocyte recognition or recognition of target cells for ADCC (by NK cells)
2. Herpes simplex: encodes a complement receptor to block complement mediated effector pathways
3. Vaccinia: complement control proteins to inhibit efficient complement activation of infected cell

Question 30

What are 4 mechanisms that pathogens use to inhibit the inflammatory response? And give and example of a virus that does each

Answer 30

1. chemokine receptor homolog: cytomegalovirus
2. inhibition of adhesion molecules to block lymphocyte trafficking to infected cells: Epstein-Barr Virus
3. TLR homologs to prevent inflam response elicited by cytokines/bac pathogens: Vaccinia
4. soluble cytokine receptor to bind up cytokines/block them from having effect: Vaccinia

Question 31

What pathogens block the Ag processing and presentation and how do they do this? (2)

Answer 31

1. herpes simplex cytomegalovirus: upregulate INF-gamma –> inhibits MHC class I
2. Herpes simplex: inhibit TAP –> no loading of peptides onto MHC class I

Question 32

What virus immunosupresses the host and how does it do this?

Answer 32

Epstein Barr by making IL-10 homologs. IL-10 homolog binds IL-10 receptor –> anti-inflammatory response created

Question 33

How does cytomegalovirus subvert immune responses?

Answer 33

1. interfere with Ag processing and presentation onto MHC class I molecules by
   
   • inhibiting TAP, blocking proteosome access to viral protein, retaining MHC class I in ER, downregulates MHC I expression
2. Interferes with NK function by down regulating MIC protein expression and making MHC class I homologs

Question 34

How does cytomegalovirus prevent Ag processing and presentation onto MHC class I molecules? (5)

Answer 34

inhibiting TAP
blocking proteosome access to viral protein
retaining MHC class I in ER
down regulates MHC I expression
destroys MHC class I

Question 35

What is a superantigen? What is their significane?

Answer 35

protein that binds alpha chain of MHC I and Beta-chain of TCR to activate T cell to produce cytokines.

They can activate 2-20% of T cells in the human body–> cytokine storm –> pathogen can evade immune response but it often results in the death of the host

Question 36

T or F: Superantigen binding to MHC and TCR is Ag specific.

Answer 36

False: it is not –> why so many T cells are able to be activated to cause a cytokine storm

Question 37

TSS can be caused by the effects of a _______

Answer 37

superantigen

Question 38

What are 2 examples of a superantigen?

Answer 38

SE and TSST-1

Question 39

In what part of the world is HIV the most widespread?

Answer 39

Sub-Saharan Africa

Question 40

What is integrase? Where is it found?

Answer 40

it is the enzyme that HIV uses to integrate into host genome and it is found inside the envelope

Question 41

What type of genome does HIV have (DNA? RNA? ss? ds?

Answer 41

dsRNA

Question 42

RNA pol lacks _____ which causes ______

Answer 42

proofreading abilities –> antigenic drift

Question 43

T or F: HIV undergoes antigenic shift

Answer 43

False: antigenic drift

Question 44

Explain why HIV is said to “efficiently” utilize its genome.

Answer 44

it uses all 3 reading frames and uses alternate splicing

Question 45

How has HIV taken advantage of human behavior?

Answer 45

it is sexually transmitted and transmitted with shared needles

Question 46

What cells does HIV target?

Answer 46

CD4 T cells

Question 47

How does HIV enter host cells?

Answer 47

binds CD4 and chemokine receptor on T cell and viral envelope fuses with cell membrane and allows viral genome to enter cell

Question 48

Describe the life cycle of HIV. (latency and activation)

Answer 48

Once the viral genome is in the cell…
Latency:
reverse transcriptase take dsRNA –> cDNA
–> cDNA enters nucleus
–> integrase inserts cDNA into host genome

Activation:
T cell activation induces some Tx of provirus (NfxB = Tx factor)
–> provirus transcripts are spliced and synthesized into Tat and Rev
–> tat amplifies Tx of viral RNA
–> rev increases transport of RNA into cytosol
–>Gag, Pol, and Env are made and assembled with viral RNA into virons
–> virons but from cell

Question 49

What is the role of Tat?

Answer 49

early HIV protein that amolifies the Tx of vrial RNA

Question 50

What is the role of Rev?

Answer 50

carries HIV RNA from the nucleus to the cytoplasm

Question 51

Describe the immune response against HIV during the first few weeks of infection.

Answer 51

initally, the immune system makes a strong B and T cell mediated responses againsts HIV, but they do not clear the infection. After this, the virus enters the latency phase in which the immune system keep the virus at bay for a number of years

Question 52

T or F: the immune response to HIV can help the virus evolve to better evade the immune system.

Answer 52

True

Question 53

Ultimately, there is _______ with a decreased immune response due to depletion of _____

Answer 53

increased viremia

CD4 T cells

Question 54

T or F: During the latency period, persons infected with HIV are symptomatic.

Answer 54

False

Question 55

At what conc of CD4 T cells/microL can a person be classified as an AIDS patient.

Answer 55

200 CD4 T cells/ microL

Question 56

AIDS is terminal and a patient with it is likely to die from ______

Answer 56

an opportunistic infection

Question 57

What are the different ways that HIV evades the immune system?

Answer 57

1. antigenic drift
2. latency
3. molecular mimicry (has Ag similar to atrocytes–> neurological issues)
4. induction of acquired immunodeficiency